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A High‐Throughput Screening Method to Identify Compounds Displaying Human Vascular Embryonic Toxicity

Journal Article · · Current Protocols in Stem Cell Biology
DOI:https://doi.org/10.1002/cpsc.93· OSTI ID:1545175
 [1];  [2];  [2];  [3]
  1. CNC‐Center for Neurosciences and Cell Biology University of Coimbra Rua Larga Coimbra Portugal
  2. Faculty of Medicine University of Coimbra Health Sciences Campus, Pólo III, Central Unit Coimbra Portugal
  3. CNC‐Center for Neurosciences and Cell Biology University of Coimbra Rua Larga Coimbra Portugal, Faculty of Medicine University of Coimbra Health Sciences Campus, Pólo III, Central Unit Coimbra Portugal
Abstract

This article describes a screening platform to identify compounds that affect human embryonic vascular development. The procedure comprises the generation of human embryonic‐like endothelial cells (ECs) from human pluripotent stem cells (hPSCs) and subsequent maturation under arterial flow conditions; the use of these cells for the high‐throughput screening of small molecules that specifically inhibit the survival of embryonic‐like ECs; the confirmation of the hits in embryonic‐like ECs cultured under flow shear stress; and final validation in mouse embryonic ECs. The embryonic‐like ECs express embryonic genes including DLL1 , EPHB2 , LYN , TEK , ID1, NRP2, CAST, FLT1, IGF1, DKK3, NIN, LEF1 , and SORBS3 . The entire screening procedure (without the validation step) can be completed within 1 month. This platform is an alternative/complement to standard animal protocols for assessing the effects of chemicals on embryonic vascular development. © 2019 by John Wiley & Sons, Inc.

Sponsoring Organization:
USDOE
OSTI ID:
1545175
Journal Information:
Current Protocols in Stem Cell Biology, Journal Name: Current Protocols in Stem Cell Biology Journal Issue: 1 Vol. 50; ISSN 1941-7322
Publisher:
Wiley Blackwell (John Wiley & Sons)Copyright Statement
Country of Publication:
Country unknown/Code not available
Language:
English

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